Scientific Opinion on Dietary Reference Values for molybdenum

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Article
Panel on Dietetic Products, Nutrition and Allergies
EFSA Journal
EFSA Journal 2013;11(8):3333 [35 pp.].
doi
10.2903/j.efsa.2013.3333
Panel members at the time of adoption
Carlo Agostoni, Roberto Berni Canani, Susan Fairweather-Tait, Marina Heinonen, Hannu Korhonen, Sébastien La Vieille, Rosangela Marchelli, Ambroise Martin, Androniki Naska, Monika Neuhäuser-Berthold, Grażyna Nowicka, Yolanda Sanz, Alfonso Siani, Anders Sjödin, Martin Stern, Sean (J.J.) Strain, Inge Tetens, Daniel Tomé, Dominique Turck and Hans Verhagen
Acknowledgements

The Panel wishes to thank the members of the Working Group on Dietary Reference Values for minerals: Carlo Agostoni, Susan Fairweather-Tait, Marianne Geleijnse, Michael Hambidge, Ambroise Martin, Androniki Naska, Hildegard Przyrembel, Alfonso Siani and Hans Verhagen for the preparatory work on this scientific opinion and EFSA staff: Anja Brönstrup for the support provided to this scientific opinion.

Contact
Type
Opinion of the Scientific Committee/Scientific Panel
On request from
European Commission
Question Number
EFSA-Q-2011-01217
Adopted
11 July 2013
Published
8 August 2013
Affiliation
European Food Safety Authority (EFSA), Parma, Italy
Note
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Abstract

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies (NDA) derived Dietary Reference Values (DRVs) for molybdenum. Molybdenum is efficiently and rapidly absorbed at a wide range of intakes, and the body is able to maintain homeostasis through the regulation of excretion via the urine. Molybdenum deficiency in otherwise healthy humans has not been observed and there are no biomarkers of molybdenum status. Various metabolic balance studies have been performed to establish molybdenum requirements. However, only one balance study, which was performed with a constant diet and under controlled conditions in adult men, was considered to be of sufficient duration. In this small study, balance was reported to be near zero when molybdenum intakes were 22 µg/day. Biochemical changes or symptoms suggestive of molybdenum deficiency were not observed, and it is possible that humans may be able to achieve molybdenum balance at even lower intakes. Data on molybdenum intakes and health outcomes were unavailable for the setting of DRVs for molybdenum. As the evidence required to derive an Average Requirement and a Population Reference Intake was considered insufficient, an Adequate Intake (AI) is proposed. Observed molybdenum intakes from mixed diets in Europe were taken into consideration in setting this value. An AI of 65 µg/day is proposed for adults; a figure that is based on molybdenum intakes at the lower end of the wide range of observed intakes. It is suggested that the adult AI also applies to pregnant and lactating women. An AI is also proposed for infants from seven months and for children based on extrapolation from the adult AI using isometric scaling and the reference body weights of the respective age groups.  

Summary

Following a request from the European Commission, the EFSA Panel on Dietetic Products, Nutrition and Allergies (NDA) was asked to deliver a scientific opinion on Dietary Reference Values (DRVs) for the European population, including molybdenum.

Molybdenum is an essential component of certain enzymes that catalyse redox reactions and contain, in addition to molybdenum, other prosthetic groups such as flavin adenine dinucleotide or haem. In humans, sulphite oxidase, xanthine oxidoreductase, aldehyde oxidase and mitochondrial amidoxime reducing component require molybdenum linked with a pterin (molybdopterin) as the cofactor. These enzymes are involved in the metabolism of aromatic aldehydes and the catabolism of sulphur-containing amino acids and heterocyclic compounds, including purines, pyrimidines, pteridins and pyridines.

In humans, a single case report of a syndrome suggestive of dietary molybdenum deficiency in a patient on total parenteral nutrition for several months has been reported, but clinical signs of molybdenum deficiency in otherwise healthy humans have not been observed. A distinct molybdenum deficiency syndrome has not been observed in animals when subjected to molybdenum restriction, despite considerable reduction in the activity of molybdoenzymes.

Water-soluble molybdates are efficiently and rapidly absorbed from the digestive tract at a wide range of intakes, and the body is able to adapt to this wide intake range by regulating excretion via the urine. Storage of molybdenum in mammals is low, and most tissue molybdenum is thought to be associated with molybdoenzymes.

There are no suitable biomarkers of molybdenum status. Biochemical changes observed in subjects with molybdopterin cofactor deficiency, a genetic disorder, or in the one subject reported with possible molybdenum deficiency, have not been observed in healthy individuals on varying levels of molybdenum intake. Low activity of molybdoenzymes in tissues, or changes in substrate/product relationships, are considered as insufficiently specific to be used as biomarkers of status.

Molybdenum is present in nearly all foods in trace amounts as soluble molybdates. Foods high in molybdenum are pulses, cereal grains and grain products, offal (liver, kidney) and nuts. Cereals and cereal-based products including bread are the major food contributors to the dietary molybdenum intake of adults. Mean molybdenum intakes, as assessed in duplicate diet or food portion studies, total diet studies and market basket studies, vary over a wide range, i.e. 58 µg/day to 157 µg/day, for adults in various European countries. Mean intakes are at or above 100 µg/day in five of the eight European countries for which data are available. Molybdenum intakes of children are only available from two European countries.

In 1993, the Scientific Committee for Food did not publish DRVs for molybdenum. More recently, other authorities have set DRVs for molybdenum and these are based on the maintenance of molybdenum homeostasis as measured in balance studies, taking into account molybdenum bioavailability from various food sources, or are based on observed molybdenum intakes with a mixed diet.

Various balance studies have been performed to establish molybdenum requirements. However, only one balance study in adults was considered to be of sufficient duration, and was performed with a constant diet and under controlled conditions. In this study carried out in four men, balance was reported to be near zero from day 49 until day 102 of the depletion period when intakes were as low as 22 µg/day. Biochemical changes or symptoms suggestive of molybdenum deficiency were not observed and the possibility that humans may be able to achieve molybdenum balance at even lower intakes cannot be excluded. Results of two balance studies with some methodological limitations were reported in children, but these studies cannot be used to derive an average molybdenum requirement for children. Data on molybdenum intakes and health outcomes were unavailable for the setting of DRVs for molybdenum.

As the evidence to derive an Average Requirement (AR), and thus a Population Reference Intake, was considered insufficient, an Adequate Intake (AI) is proposed. An AI of 65 µg/day is proposed for adult men and women based on mean molybdenum intakes at the lower end of the wide range of observed intakes from mixed diets in Europe. Given the scarcity of data on molybdenum intakes in pregnant and lactating women, it is suggested that the adult AI also applies to pregnant and lactating women. For infants from seven months and children, it was decided that an AR could not be established, and an AI is proposed based on extrapolation from the adult AI using isometric scaling and reference body weights of the respective age groups. The respective AIs vary between 10 µg/day in infants aged 7-11 months and 65 µg/day in adolescent boys and girls.

Keywords
molybdenum, Adequate Intake, Dietary Reference Value
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Number of Pages
35